A sensitive method for light microscopic localization of brain receptors by in vitro autoradiography was developed previously in this laboratory. By this method we have mapped the locations of opiate receptors in the brains of rats and other vertebrates, including primates. Comparisons of tritiated naloxone binding with tritiated enkephalin binding have reinforced the notion of opiate receptor subtypes. These have been followed ontogenetically and phylogenetically and have been related to the dopamine system in the striatum. The possibility of pharmacological manipulation of receptor distribution is being examined. Applications are being pursued for the study of receptors and biologically active peptides and enzymes in unfixed human brains obtained at autopsy. The unfixed, cryostat-cut tissue is amenable for concurrent study of metabolic and functional mapping by 2-deoxy-D-glucose. For example, we have compared phencyclidine (PCP) receptor localization patterns with patterns of altered brain metabolic activity produced by phencyclidine "anesthesia". The technique is used also for studies related to sleep, circadian rhythms and drug-induced sedation.